Context: Many psychological problems including stress, anxiety, insomnia, depression, frustration, denial, anger, and fear emerged during coronavirus disease 2019 (COVID-19) outbreak. Aims: This study was done to assess the prevalence and associated factors of depression, anxiety, stress, insomnia, and fear experienced by health-care workers (HWs) during COVID-19 in Nepal. Settings and Design: This was web-based analytical cross-sectional study conducted among health-care workers from December 27, 2020, to February 28, 2021, all over Nepal. Subjects and Methods: All the HWs including doctors, nurses, and allied health-care professional from 7 provinces were selected using convenience sampling technique. Data collection was done using the validated questionnaires. Statistical Analysis Used: Univariate and binary logistic regression analyses were performed to find the association between the different variables. Statistical significance was set at P < 0.05. Results: A total of 608 HWs completed the survey with a mean age of 30.82 ± 6.68. About 27% had symptoms of depression, 28% anxiety, 10% stress, 18% insomnia, and 49.8% fear of COVID-19. Resident doctors and health workers who had bachelor level of education and working experience <2 years were significantly associated with higher odds of experiencing depression and anxiety. Health workers working 2–5 years and with more than 5 years' experience had significantly lower odds of experiencing fear. History of tobacco use or medical condition had significantly higher odds of experiencing depression, anxiety, stress, insomnia, and fear. Conclusions: This study concluded that the prevalence of depression, anxiety, insomnia, and fear was found to be high. Resident doctors and health workers with bachelor level of education, working experience <2 years, and history of medical condition were significantly associated with experiencing adverse mental health outcomes.